Intramuscular ziprasidone treatment of acute psychotic agitation in elderly patients with schizophrenia.

OBJECTIVE: Intramuscular (i.m.) ziprasidone treatment has been shown to be effective and well tolerated in reducing the symptoms of acute psychosis in adults. Few data are available as to safety in the elderly. The growing utilization of health services by elderly psychiatric patients warrants an evaluation in this population. METHOD: Consecutive elderly patients (60 years of and older) admitted to a psychogeriatric ward in a large, university-affiliated tertiary psychiatric center were treated by i.m. ziprasidone for acute psychotic agitation. Patients received three days of flexible-dose i.m. ziprasidone. After an initial dose of 10-20 mg, a subsequent dose of 10-20 mg could be given after 12 hours if needed (maximum daily dose: 40 mg). RESULTS: All treatment emergent side effects and adverse events along with the investigators' assessments of severity were systematically recorded as the primary outcome. The Brief Psychiatric Rating Scale (BPRS) and the Behavioral Activity Rating Scale (BARS) were the secondary outcomes. Twenty-one patients, six male and 15 female, mean age 71.4 +/- 1.3 years (range: 60-81 years) were enrolled. All had completed the three days i.m. ziprasidone treatment. There was one adverse event in a patient with untreated benign prostatic hypertrophy who developed urinary retention. Two side effects of mild severity that resolved spontaneously were observed: blurred vision and sedation. The BPRS decreased by 26.8 points after three days of treatment (p = 0.001). The BARS score, reflecting agitation, decreased significantly after each injection, reaching maximal decrease of 2.14 points at completion of study (p = 0.001). CONCLUSION: Intramuscular ziprasidone in this series of elderly patients suggests acceptable safety and efficacy in the management of acute psychotic agitation among elderly patients with schizophrenia.     

Poor Intraoperative Blood Glucose Control Is Associated with a Worsened Hospital Outcome after Cardiac Surgery in Diabetic Patients

Background: Tight perioperative control of blood glucose improves the outcome of diabetic patients undergoing cardiac surgery. Because stress response and cardiopulmonary bypass can induce profound hyperglycemia, intraoperative glycemic control may become difficult. The authors undertook a prospective cohort study to determine whether poor intraoperative glycemic control is associated with increased intrahospital morbidity.

Methods: Two hundred consecutive diabetic patients undergoing on-pump heart surgery were enrolled. A standard insulin protocol based on subcutaneous intermediary insulin was given the morning of the surgery. Intravenous insulin therapy was initiated intraoperatively from blood glucose concentrations of 180 mg/dl or greater and titrated according to a predefined protocol. Poor intraoperative glycemic control was defined as four consecutive blood glucose concentrations greater than 200 mg/dl without any decrease in despite insulin therapy. Postoperative blood glucose concentrations were maintained below 140 mg/dl by using aggressive insulin therapy. The main endpoints were severe cardiovascular, respiratory, infectious, neurologic, and renal in-hospital morbidity.

Results: Insulin therapy was required intraoperatively in 36% of patients, and poor intraoperative glycemic control was observed in 18% of patients. Poor intraoperative glycemic control was significantly more frequent in patients with severe postoperative morbidity (37% vs. 10%; P < 0.001). The adjusted odds ratio for severe postoperative morbidity among patients with a poor intraoperative glycemic control as compared with patients without was 7.2 (95% confidence interval, 2.7-19.0).     

Pathophysiological aspects of brain edema

Summary Two mayor types of brain edema, related to two different pathomechanisms, can be recognized: 1)cytotoxic type-where the main feature is the swelling of cellular elements of brain parenchyma and 2)vasogenic type-where an increased vascular permeability leading to accumulation of edema fluid inthe extracellular spaces plays the principal role. In this type of edema, there is a close interrelationship between extravasation of serum proteins and retention of water in the brain tissue. In theischemic brain edema both cytotoxic and vasogenic mechanisms are involved. A biphasic opening of the blood-brain barrier, associated with vasogenic edema, is observed following release of major cerebral artery occlusion. The first opening of the barrier is related to a reactive hyperemia which follows promptly recirculation. The second opening, recognizable after a delay, is associated with a severe ischemic brain tissue injury.Dedicated to Prof. F. Seitelberger on the occasion of his seventieth birthday     

Pharmacokinetics of mycophenolate mofetil in stable pediatric liver transplant recipients receiving mycophenolate mofetil and cyclosporine.

There are few pharmacokinetic data for mycophenolate mofetil (MMF) when used in combination with cyclosporine (CsA) in pediatric liver transplant recipients. The aim of this study was to assess the pharmacokinetics of MMF in stable pediatric liver transplant patients and estimate the dose of MMF required to provide a mycophenolic acid (MPA) exposure similar to that observed in adult liver transplant recipients receiving the recommended dose of MMF (target area under the plasma concentration-time curve from 0 to 12 hours [AUC(0-12)] for MPA of 29 mug.hour/mL in the immediate posttransplantation period and 58 microg x hour/mL after 6 months). A 12-hour pharmacokinetic profile was collected for 8 pediatric patients (mean age 20.9 months) on stable doses of MMF and CsA who had received a liver transplant > or = 6 months prior to entry and who had started on MMF within 2 weeks of transplantation. Mean MMF dosage was 285 mg/m(2) (range, 200-424 mg/m(2)). Of 8 patients, 7 had a MPA AUC(0-12) (range, 11.0-37.2 microg x hour/mL) well below the target. One patient had an AUC(0-12) > or = 58 microg x hour/mL but was considered an outlier and was excluded from analyses. Mean MPA AUC(0-12) and maximum plasma concentration values were 22.7 +/- 10.5 microg x hour/mL and 7.23 +/- 3.27 microg/mL, respectively; values normalized to 600 mg/m(2) (the approved pediatric dose in renal transplantation) were 47.0 +/- 21.8 microg x hour/mL and 14.5 +/- 4.21 microg/mL. In conclusion, assuming that MPA exhibits linear pharmacokinetics, when used in combination with CsA, a MMF dose of 740 mg/m(2) twice daily would be recommended in pediatric liver transplant recipients to achieve MPA exposures similar to those observed in adult liver transplant recipients. This finding should be confirmed by a prospective trial.     

Local excision for ypT2 rectal cancer--much ado about something.

BACKGROUND: The role of local excision for pT2 distal rectal cancer has been challenged because of the observation of high rates of lymph node metastases and local failure. However, neoadjuvant chemoradiation therapy (CRT) has led to increased local disease control and significant tumor downstaging, possibly decreasing rates of lymph node metastases. In this setting, a possible role for local excision of ypT2 has been suggested. METHODS: A total of 401 patients with distal rectal cancer underwent neoadjuvant CRT. Tumor response assessment was performed after at least 8 weeks from CRT completion. One hundred and twelve patients with complete clinical response were not immediately operated on and were excluded from the study, and 289 patients with incomplete clinical response were managed by radical surgery. Patients with final pathological stage ypT2 were analyzed to determine the risk of unfavorable pathological features that could represent unacceptable risk for local failure after local excision. RESULTS: Eighty-eight (30%) patients had ypT2 rectal cancer. Final ypT status was not associated with pretreatment radiological staging (p = 0.62). ypT status was significantly associated with the risk of lymph node metastases, risk of perineural and vascular invasion, and recurrence (p = 0.001). Lymph node metastases were present in 19% of patients with ypT2 rectal cancer. The risk of lymph node metastases in ypT2 was associated with the presence of perineural invasion (47% vs 4%; p = <0.001), vascular invasion (59% vs 6%; p < 0.001), and decreased mean interval CRT surgery (12 vs 18 weeks; p < 0.001), but not with mean tumor size (3.2 vs 3.1 cm; p = 0.8). Disease-free and overall survival rates were significantly better for patients with ypT2N0 (p = 0.02 and 0.006, respectively). Fifty-five (63%) patients with ypT2 had at least one unfavorable pathological feature for local excision (lymph node metastases, vascular or perineural invasion, mucinous type or tumor size >3 cm). CONCLUSION: Lymph node metastases were present in 19% of patients with ypT2 and were significantly associated with poor overall and disease-free survival rates. The risk of lymph node metastases could not be predicted by radiological staging or tumor size. Radical surgery should be considered the standard treatment option for ypT2 rectal cancer after CRT.     

Depressive Symptoms Among HIV Positive Men: Life Stress,Coping, and Social Support1

The significance of life stress, coping, and social support was examined in relation to depressive symptomatology in a sample of 160 asymptomatic and mildly symptomatic HIV-antibody-positive (HIV+) men. The participants (mean age = 32 years) were interviewed about the life stress that they had experienced in the previous 6     

The development of food allergy after liver transplantation.

The acquisition of new food allergy after orthotopic liver transplantation is now a well described phenomenon, mainly reported in children. The etiology of this phenomenon is at present unclear, but has been ascribed by some to tacrolimus treatment. Here we report a case of liver transplant acquired food allergy (LTAFA) in a child who received a split liver graft. The case is remarkable for the absence of new food allergy in the adult recipient of the same graft. This suggests that host-specific factors play an important role in the development of food allergy after liver transplantation, and emphasizes the predisposition that children have toward this phenomenon. Possible mechanisms underlying the development of food allergy after liver transplantation are discussed. In conclusion, tacrolimus treatment alone cannot account for LTAFA. Host factors such as the maturity of immune regulatory mechanisms are likely to play a critical role in the development of new food allergy after a liver transplant.     

Selective Postsynaptic Inhibition of Tonic-firing Neurons in Substantia Gelatinosa by μ-Opioid Agonist

Background: Spinal substantia gelatinosa (SG) is a site of action of administered and endogenous opioid agonists and is an important element in the system of antinociception. However, little is known about the types of neurons serving as specific postsynaptic targets for opioid action within the SG. To study the spinal mechanisms of opioidergic analgesia, the authors compared the action of [mu]-opioid agonist [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin (DAMGO) on SG neurons with different intrinsic firing properties.

Methods: Whole cell patch clamp recordings from spinal cord slices of Wistar rats were used to study the sensitivity of SG neurons to DAMGO.

Results: Three groups of neurons with distinct distributions in SG were classified: tonic-, adapting-, and delayed-firing neurons. DAMGO at 1 [mu]m concentration selectively hyperpolarized all tonic-firing neurons tested, whereas none of the adapting- or delayed-firing neurons were affected. The effect of DAMGO on tonic-firing neurons was due to activation of G protein-coupled inward-rectifier K+ conductance, which could be blocked by 500 [mu]m Ba2+ and 500 [mu]m Cs+ but increased by 50 [mu]m baclofen. As a functional consequence of DAMGO action, a majority of tonic-firing neurons changed their pattern of intrinsic firing from tonic to adapting.